CENTRAL MONOAMINES IN ACUTE-PHASE REACTION

急性期反应中的中心单胺

• 批准号: 3405545
• 负责人: CLARK M BLATTEIS
• 金额: $ 14.1万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-09-01 至 1993-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3405545
• 关键词: acetaminophen; adrenergic receptor; body temperature regulation; central nervous system; histamine; hyperthermia; microdialysis; norepinephrine; preoptic areas; prostaglandin E; psychoneuroimmunology; serotonin

Recently, we found that the thermal response to norepinephrine (NE) differed unexpectedly when it was microdialyzed, rather microinjected, into the preoptic area (PO) of conscious guinea pigs; i.e., NE produced a fall rather than a rise in core temperature (Tco). Our studies showed that the Tco rise following microinjected NE was due largely to prostaglandin E2 (PGE2) released as a result of tissue injury caused by the microinjection procedure itself, and was not due to the drug, i.e., it was artefactual. Our microdialysis data further suggested that there exists a functional antagonism between endogenous NE and PGE2; it appeared that their relative concentrations in the PO might mutually influence Tco. The first aim of this proposed study, therefore, is to evaluate this apparent functional NE- PGE2 antagonism. Various other studies have lately indicated that different responses to NE administration in vivo or application in vitro are activated depending on the NE dose, and that these different effects are mediated by different noradrenergic receptor subtypes. Subtype populations and densities have also been shown to be inconstant, subject to change under certain conditions. Since the different thermoreregulatory effects of centrally administrated NE have also been reported to depend on dosage and various other conditions, the second aim of this proposed study is to determine whether the direction of thermal responses to NE is adrenoceptor subtype-dependent, and to investigate the influence on the thermal response of selected experimental conditions. The third aim of the present study is to delineate the function(s) of NE during fever in the context of the above hypotheses, since the literature on the role of central NE in the febrile response, though extensive, is inconclusive, probably because of the variability of experimental conditions used in all the studies. Evaluation of the intrinsic thermoregulatory effects of this transmitter will be made easier by the availability now of more specific receptor agonists and antagonists and by the use of microdialysis, which minimizes the confounding effects of traumatic reactions that affect other modes of drug administration. The results of this study should help to resolve the discrepancies among earlier findings and clarify the role of NE in the central control of body temperature. They may also be pertinent to other functions in which hypothalamic NE has been implicated, e.g., in the interactions between the neuroendocrine and immune systems.

最近，我们发现去甲肾上腺素(NE)引起的体温反应。 当它被微透析，而不是显微注射时，出人意料地不同 清醒豚鼠的视前区(PO)，即去甲肾上腺素(NE)产生下坠 而不是核心温度(TCO)的上升。我们的研究表明， 微量注射去甲肾上腺素后TCO升高的主要原因是前列腺素E2 (PGE2)因显微注射造成组织损伤而释放 程序本身，不是由于药物，也就是说，它是人为的。 我们的微透析数据进一步表明存在一种功能性的 内源性去甲肾上腺素和前列腺素E_2的拮抗作用 PO中的浓度可能会相互影响TCO。的第一个目标 因此，这项拟议的研究旨在评估这一明显的功能NE- PGE2拮抗作用。最近的各种其他研究表明， 体内和体外对去甲肾上腺素的不同反应 根据去甲肾上腺素的剂量而被激活，这些不同的影响 由不同的去甲肾上腺素受体亚型介导。亚型 人口和密度也被证明是不稳定的，受 在某些条件下会发生变化。由于不同的温度监管 据报道，集中管理的NE的效果也取决于 剂量和各种其他条件，这项拟议研究的第二个目的 是确定对NE的热响应方向是否为 肾上腺素能受体亚型依赖，并探讨其对 选定实验条件下的热响应。的第三个目标 本研究旨在探讨去甲肾上腺素(NE)在发热中的作用(S)。 以上假设的来龙去脉，自文献介绍以来的作用 中枢NE在发热反应中的作用，虽然广泛，但尚不确定， 可能是因为所有实验条件的变化性 这些研究。对其内在体温调节作用的评估 变送器将变得更容易，因为现在有了更具体的 受体激动剂和拮抗剂，并通过使用微透析， 最大限度地减少影响他人的创伤反应的混杂影响 三是药品管理模式。这项研究的结果应该有助于 解决早期发现之间的差异，并澄清NE的作用 对体温的中央控制。它们也可能与以下内容有关 其他与下丘脑去甲肾上腺素有关的功能，例如 神经内分泌和免疫系统之间的相互作用。